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Performance at Preoperative Stair-Climbing Test IsAssociated With Prognosis After PulmonaryResection in Stage I Non-Small Cell Lung CancerAlessandro Brunelli, MD, Cecilia Pompili, MD, Rossana Berardi, MD,Paola Mazzanti, MD, Azzurra Onofri, MD, Michele Salati, MD, Stefano Cascinu, MD,and Armando Sabbatini, MD

Division of Thoracic Surgery and Medical Oncology, Ospedali Riuniti Ancona, Ancona, Italy

Background. This investigation evaluated whether theperformance at a preoperative symptom-limited stair-climbing test was a prognostic factor in resected patho-logic stage I non-small cell lung cancer (NSCLC).

Methods. Observational analysis was performed on aprospective database that included 296 patients whounderwent pulmonary lobectomy for pathologic stage T1N0 or T2 N0 NSCLC (2000 to 2008). Patients who receivedinduction chemotherapy were excluded. Survival wascalculated by the Kaplan-Meyer method. The log-ranktest was used to assess differences in survival betweengroups. The relationships between survival and baselineand clinical variables were determined by Cox multivar-iate analyses.

Results. Median follow-up was 43 months. The bestcutoff associated with prognosis was an 18-meter stair

climb. Median (months) survival and 5-year survival of

Address correspondence to Dr Brunelli, Via S. Margherita 23, An-cona 60129, Italy; e-mail: brunellialex@gmail.com.

© 2012 by The Society of Thoracic SurgeonsPublished by Elsevier Inc

patients who climbed more than 18 meters were signifi-cantly longer than those who climbed less than 18 meters(97 vs 74; 77% vs 54%, p � 0.001). Cox regression model(hazard ratio) showed that climbing more than 18 meters(0.5; p � 0.003), diffusion capacity of the lung for carbonmonoxide (0.98; p � 0.02), and pT stage (1.8; p � 0.02)were independent prognostic factors. Patients whoclimbed less than 18 meters had increased deaths fromcancer (24% vs 15%, p � 0.1) or other causes (19% vs 9%,p � 0.02).

Conclusions. Preoperative cardiopulmonary fitness is asignificant prognostic factor in patients after resection forearly-stage NSCLC. Interventions aimed at improvingexercise tolerance can be useful to improve long-termprognosis after NSCLC operations.

(Ann Thorac Surg 2012;93:1796–801)

© 2012 by The Society of Thoracic Surgeons

Lung cancer patients generally have a reduced exer-cise tolerance compared with the general population

[1, 2]. Lung resection may be associated with a varyingdegree of functional impairment that can further de-crease aerobic capacity and predispose the patient topostoperative morbidity and death as well as impairedquality of life [3–5]. To date, however, scant informationhas been published regarding the association betweenpreoperative fitness and long-term survival of lung can-cer patients [6, 7]. The objective of this investigation wasto evaluate whether preoperative exercise tolerance mea-sured with a symptom-limited stair-climbing test was areliable prognosticator associated with long-term sur-vival in stage I non-small cell lung cancer (NSCLC)patients undergoing pulmonary lobectomy. The rationaleof this investigation was to find a prognosticator thatcould be modifiable through the institution of specificrehabilitation programs [8–12].

Accepted for publication Feb 23, 2012.

Presented at the Poster Session of the Forty-eighth Annual Meeting ofThe Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 28–Feb 1, 2012.

Patients and Methods

This was an observational analysis performed on a pro-spective database. The study was approved by the localInstitutional Review Board. All patients gave their in-formed consent to participate in the institutional pro-spective database and for the use of their data forresearch and clinical purposes. A total of 296 consecutivepatients undergoing pulmonary lobectomy and system-atic lymph node dissection [13] for pathologic stage I (pT1or pT2-N0 only) NSCLC and with complete follow-upwere analyzed (2000 to 2008). Patients who received induc-tion chemotherapy were excluded. No patients in this seriesunderwent adjuvant chemotherapy or radiotherapy. Exclu-sion criteria were more advanced pathologic stage, incom-plete resections, induction chemotherapy, and inability toperform the preoperative stair-climbing test (40 patientsduring the same period).

Patients were staged according to the American JointCommittee on Cancer, Seventh Edition guidelines [14].

Patients underwent radical resection by board-certifiedthoracic surgeons generally through a muscle-sparing,nerve-sparing [15] lateral thoracotomy, and as a rule,were extubated in the operating room and managed in adedicated thoracic surgery unit. Intensive care admission

was occasionally planned for patients with compromised

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preoperative function (ie, peak maximum oxygen con-sumption � 12 mL/kg/min) and otherwise reserved forpatients with severe postoperative complications whoneeded active life support treatment [16].

Postoperative management was standardized and in-cluded chest physiotherapy, early mobilization, physicalrehabilitation, and adequate paravertebral or systemicanalgesic therapy, which was titrated to keep the visualanalog pain score below 4 (on a scale from 0 to 10) duringthe first 48 to 72 hours.

Stair-Climbing TestAll patients performed a preoperative symptom-limitedstair-climbing test as a part of their routine preoperativefunctional evaluation [17, 18]. The stair-climbing test wasusually performed within 1 week of the operation. Ourhospital has 16 flights of stairs, each consisting of 11steps. Each step is 0.155 meters high. Patients were askedto climb, at a pace of their own choice, the maximumnumber of steps and to stop only for exhaustion, limitingdyspnea, leg fatigue, or chest pain. All patients wereaccompanied by a physician, and the patient’s pulse rateand capillary oxygen saturation were monitored bymeans of a portable pulse oximeter with a finger probe.All tests were performed on room air.

Follow-up was obtained through routine office visits,by telephone contact, or by data retrieved from theRegional Health Care System database. All patients weremonitored through April 2011. The cause of death wasrecorded.

Data AnalysisThe following baseline and tumor variables were testedfor a possible association with survival: age, sex, Charl-son Comorbidity Index (CCI), body mass index (BMI),American Society of Anesthesiologist (ASA) score, East-ern Cooperative Oncology Group (ECOG) score, preop-erative hemoglobin concentration, forced expiratory vol-ume in 1 second (FEV1 %), diffusion capacity of the lungfor carbon monoxide (Dlco %), FEV1/forced vital capac-ity (FVC) ratio, history of coronary artery disease (CAD),preoperative hemoglobin level, pT stage (pT1 vs pT2),histology (adenocarcinoma vs squamous vs others), andaltitude reached at stair-climbing test.

For the purpose of this study, a threshold effect wassearched for the altitude at the stair-climbing test byperforming log-rank tests for multiple cutoff values. Thevalue with the highest association with survival wasselected. Survival was defined as the interval betweenthe surgical resection and death or last contact. Patientswho were not reported as having died at the time of theanalysis were censored at the date they were last knownto be alive. The Cox multivariate proportional hazardregression model was used to evaluate the effects of theprognostic factors on survival. Predictors with p values ofless than 0.2 at univariable analysis were used in amultivariable Cox’s proportional hazards model.

Survival distribution was estimated by the Kaplan-Meier method. Significant differences in probability of

surviving between the strata were evaluated by log-rank

test. Hazard ratios (HR) and 95% confidence intervals(CI) were estimated from regression coefficients. A sig-nificant level of 0.05 was chosen to assess the statisticalsignificance. A p value of less than 0.05 was regarded assignificant. All statistical tests were performed on Stata9.0 software (Stata Corp, College Station, TX).

Results

Patient characteristics are summarized in Table 1. Me-dian follow-up was 43 months. The average altitudereached at preoperative stair climb test was 20 meters.Testing for a threshold effect showed that 18 meters wasthe best cutoff associated with long-term survival. Com-pared with patients who climbed less than 18 meters,patients who climbed more than 18 meters had signifi-cantly longer median survival of 97 (95% CI, 89 to 105)months vs 74 (95% CI, 63 to 85) months and 5-yearsurvival of 77% vs 54% (p � 0.001; Fig 1).

Table 2 reports the results of the univariable analysisfor overall survival. Along with the altitude reached onthe stair-climbing test, the following variables were as-sociated with overall survival (p � 0.2) and were used inthe multivariable analysis: age, sex, CCI, FEV1%, Dlco %,pT stage, preoperative hemoglobin level, and ECOGscore.

The Cox proportional hazards regression modelshowed that climbing more than 18 meters (HR, 0.5; p �0.003), Dlco (HR, 0.98; p � 0.02), and pT stage (HR, 1.8;p � 0.02) were independent prognosticators significantlyassociated with survival.

The pT1 stage patients who climbed more than 18meters lived significantly longer than those who did not(85% vs 53%, p � 0.0009; Fig 2). This difference in pT2stage patients was still present but less evident (71% vs

Table 1. Characteristics of the 282 Study Patients

Variables a Result

Age, years 68 (9.8)Male sex, No. (%) 218 (77)FEV1 % 87.9 (19)Dlco % 78.6 (17.8)FEV1/FVC ratio 0.7 (0.1)Pre-op hemoglobin level, g/dL 13.8 (1.7)Coronary artery disease, No. (%) 26 (9)ASA score 2.2 (0.5)ECOG score 0.7 (0.7)Stair-climbing height, meters 20 (4.3)Side of resection, right, No. (%) 147 (52)Site of resection, upper, No. (%) 187 (67)pT1 stage, No. (%) 118 (42)

a Continuous data are expressed as mean (standard deviation) andcategoric data as indicated.

ASA � American Society of Anesthesiologists; Dlco � diffusioncapacity of the lung for carbon monoxide; ECOG � Eastern Cooper-ative Oncology Group; FEV1 � forced expiratory volume in 1 second;FVC � forced vital capacity.

55%, p � 0.15; Fig 3).

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Patients who climbed less than 18 meters had highercancer-specific (24% vs 15%, p � 0.1) and other-causemortality rates (19% vs 9%, p � 0.02). Figure 4 shows thecancer-specific survival for patients who climbed morethan 18 meters compared with those who climbed lessthan 18 meters. The log-rank test showed a significantdifference between the two groups (p � 0.04).

Comment

The association between exercise tolerance and progno-sis in cancer survivors has been rarely reported. Regularmoderate-intensity exercise is known to be associatedwith a 30% to 50% reduction in the risk of cancer-specific

Fig 1. Kaplan-Meier overall survival estimates are shown for stage Inon-small cell lung cancer patients who underwent surgical resec-tion according to their performance on the preoperative stair-climb-ing test. High: � 18 meters (solid line). Low: � 18 meters (dashedline). Log-rank test p � 0.003.

Table 2. Results of the Univariable Analysis to TestAssociation of Several Variables With Overall Survival

Variables p Value

Sex 0.14 a

Age 0.0002b

Charlson Comorbidity Index 0.18b

FEV1 % 0.1b

Dlco % 0.002b

Stair climb height 0.0005b

Coronary artery disease 0.7 a

Hemoglobin level 0.18b

ASA 0.8b

ECOG 0.04b

Histology 0.6 a

pT stage 0.02 a

a By log-rank test. b By univariable Cox proportional hazardregression.

ASA � American Society of Anesthesiologists; Dlco � diffusion

capacity of the lung for carbon monoxide; ECOG � Eastern Cooper-ative Oncology Group; FEV1 � forced expiratory volume in 1 second.

mortality and all-cause mortality after a diagnosis ofearly breast or colorectal cancer [19–22]. Two studieshave evaluated the prognostic importance of exercisetolerance in lung cancer. Kasymjanova and colleagues [6]assessed the prognostic value of the 6-minute walk test inpatients with inoperable NSCLC and found that a walkdistance of 400 meters or more was the only variablesignificantly associated with survival. Jones and col-leagues [7] investigated the prognostic value of aerobiccapacity before lung cancer operations and found thatlow peak maximum oxygen consumption was associatedwith poorer survival.

The objective of the present study was to verifywhether preoperative fitness in patients with radical

Fig 2. Kaplan-Meier overall survival estimates are shown for patho-logic pT1 N0 stage non-small cell lung cancer patients who under-went surgical resection according to their performance on the preop-erative stair-climbing test. High: � 18 meters (solid line). Low: � 18meters (dashed line). Log-rank test p � 0.009.

Fig 3. Kaplan Meier overall survival estimates are shown for patho-logic pT2 N0 stage non-small cell lung cancer patients who under-went surgical resection according to their performance on the preop-erative stair-climbing test. High: � 18 meters (solid line). Low: � 18

meters (dashed line). Log-rank test p � 0.2.

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resection for stage I NSCLC was associated with long-term survival after pulmonary lobectomy. We evaluatedexercise tolerance by a symptom-limited stair-climbingtest, a form of constant work rate maximal exercise that isroutinely used in our unit for risk-stratification andoperability selection [17]. The stair-climbing test is areliable test to predict postoperative early morbidity anddeath [23], and in this study we used it to investigatelong-term survival.

We found that median overall survival was 23 monthslonger in patients who climbed higher than 18 meterscompared with those who climbed to a lower altitude.The effect of exercise tolerance was independent of otherconfounders when adjusted in a multivariable analysisand can be partly explained by increased deaths fromcancer recurrence and other causes (such as cardiopul-monary complications). In fact, cancer-specific survivalwas also longer in patients who climbed more than 18meters.

These findings may have important clinical implica-tions because exercise tolerance is a modifiable prognos-ticator. Structured rehabilitation programs may improveaerobic capacity in the preoperative setting [2, 8–12, 24, 25]with the potential to influence residual quality of life andlong-term survival.

Patients who are in better clinical condition before theoperation can have a lower risk of early and late cardio-pulmonary complications after the operation. This wouldexplain the reduction in deaths from causes other thancancer recurrence. However, a better performance at thestair-climbing test was also associated with a longercancer-specific survival and with the reduction in cancer-related deaths. The beneficial effects of physical activityand physical function on cancer recurrence has been thefocus of recent investigations and may be related to a

Fig 4. Kaplan Meier cancer-specific survival estimates are shown forpathologic stage I stage non-small cell lung cancer patients who un-derwent surgical resection according to their performance on the pre-operative stair-climbing test. High: � 18 meters (solid line). Low: �18 meters (dashed line). Log-rank test p � 0.04.

reduction in body weight and composition, beneficial

changes in metabolic and sex hormones, growth factors,adipokines, immune function, or inflammation [25–27].

Although this study includes a homogeneous sizeablesample of patients undergoing pulmonary lobectomy in asingle center with standardized procedures and path-ways of care and with a long follow-up, it may have somelimitations:

● We included pathologic stage I NSCLC (T1–2N0)only. Further studies are warranted to confirm ourfindings in other stages of disease.

● The study included patients undergoing radicalpulmonary lobectomy performed through a mus-cle-sparing lateral thoracotomy. The interactionbetween exercise and prognosis for other type ofresections or surgical accesses (including video-assisted thoracoscopic procedures) needs to beconfirmed.

● Exercise tolerance was evaluated through stair-climbing test. We found a cutoff of 18 meters inour setting was the best prognosticator. Structuraldifferences across different hospital makes thiscutoff value difficult to standardize and warrantsfuture confirmation by independent investigators.

● We only assessed preoperative exercise tolerance.Although preoperative and postoperative fitnesslevels may be correlated [28], their relationshipacross time may not be linear, and the influence ofthis interaction on prognosis may deserve furtherinvestigations.

● Owing to the retrospective nature of the study, wecannot completely rule out the possibility thatlower levels of exercise tolerance may reflect otheroccult predictors for poor prognosis. For instance,the occurrence of postoperative cardiopulmonarycomplications, which may be associated with poorfitness, was associated in this series with poorerlong-term 5-year survival of 61% for complica-tions vs 75% for no complications (log-rank testp � 0.01). However, our findings remained un-changed after adjusting for other potentialprognosticators.

There is a cumulating body of data showing a potentialassociation between physical fitness after cancer diagno-sis and treatment and survival. All of these data, such asthe present findings, are observational; therefore, cause-and-effect cannot be assumed. These preliminary find-ings look promising, but the only way to answer whetherincreased physical activity can reduce recurrence ordeaths due to cancer is to design randomized controlledclinical trials [29].

In conclusion, we found that preoperative cardiopul-monary fitness was a significant prognosticator in pa-tients operated on for early-stage lung cancer. Exercisetolerance may influence physiologic outcomes associatedwith cancer, such as immune function, body weight andcomposition, insulin regulation, and the metabolic syn-drome, that can potentially affect survival. Interventionsaimed at improving exercise tolerance can possibly im-

prove long-term prognosis after lung cancer operations.

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INVITED COMMENTARY

A simple test such as stair-climbing to predict prognosisafter surgery for early stage lung cancer has great appeal.Most thoracic surgeons are familiar with the use ofstair-climbing to determine the fitness of patients forsurgery. A simple test (stair-climbing) accompanied bythe surgeon’s intuition, experience, and a few objectivetests has been a valuable tool for surgeons.

The simple stair-climb is usually not standardized, lacksobjective assessment, and is not scientific. Despite theselimitations, few deny its usefulness in patient assessment.

address these limitations and improve our understandingof this test relative to tolerating surgery.

The authors [1] have now taken another step and haveused this simple test to predict prognosis after surgeryfor early stage lung cancer. It would be too easy to dismissthis finding as oversimplified. The observation of a corre-lation between stair-climbing and prognosis begs furtherquestions. Is it reproducible? What is stair-climbing mea-suring, or is it just a surrogate for something else?

Larger numbers of patients are required to confirm

these findings. Can this test predict outcome in advanced

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